Abstract:
BACKGROUND:Intravenous temsirolimus, an inhibitor of the mammalian target of rapamycin (mTOR), is approved for the treatment of advanced renal cell carcinoma (RCC). Sirolimus, the principal metabolite of temsirolimus in humans, also exhibits mTOR inhibitory activity. OBJECTIVE:The purpose of this study was to compare the pharmacokinetics of temsirolimus and its metabolite, sirolimus, among patients with RCC not receiving dialysis and those receiving hemodialysis. METHODS:This was a single-center, unblinded, single-dose study. Patients with histologically confirmed metastatic RCC were eligible. A single 25-mg dose of temsirolimus was administered as a 30-minute intravenous infusion during the first round of chemotherapy. Blood samples were drawn at 0 (predose), 0.5 (end of infusion), 1.5, 2.5, 5.5, 24, 72, and 144 hours after infusion. In patients receiving hemodialysis, an additional blood sample was drawn 1 hour after each treatment to compare pre- and postconcentration. Temsirolimus concentrations were assayed in blood using HPLC coupled to mass spectrometry. Pharmacokinetic parameters (C(max), T(max), t((1/2)), AUC(0-infinity), total body clearance, volume of distribution at steady state, AUC ratio [the ratio of sirolimus to temsirolimus AUCs], and AUC sum [the algebraic sum of temsirolimus and sirolimus AUCs]) were calculated and analyzed statistically. RESULTS:In total, 13 consecutive patients (11 men and 2 women; 11 not receiving dialysis and 2 receiving hemodialysis) were included. No patient refused to participate in the study. Of those not receiving dialysis, the median age was 54 years (range, 36-77 years), and of those receiving hemodialysis, the median age was 60.5 years (60-61 years). There were no significant between-group differences in the pharmacokinetic parameters of temsirolimus and sirolimus. Moreover, in patients receiving hemodialysis, blood drug concentrations assessed immediately before hemodialysis were similar to those assayed 1 hour after the treatment. CONCLUSION:This study found that after single-dose administration of 25 mg of temsirolimus as a 30-minute intravenous infusion, neither temsirolimus nor sirolimus concentrations were significantly affected in these patients with RCC receiving hemodi-alysis compared with those not receiving dialysis.
journal_name
Clin Therjournal_title
Clinical therapeuticsauthors
Lunardi G,Armirotti A,Nicodemo M,Cavallini L,Damonte G,Vannozzi MO,Venturini Mdoi
10.1016/j.clinthera.2009.08.018subject
Has Abstractpub_date
2009-08-01 00:00:00pages
1812-9issue
8eissn
0149-2918issn
1879-114Xpii
S0149-2918(09)00301-4journal_volume
31pub_type
杂志文章abstract:OBJECTIVE:This study evaluated the efficacy and tolerability of glimepiride in patients with type 2 diabetes mellitus that was inadequately controlled with a combination of immediate- or extended-release metformin and a thiazolidinedione. METHODS:This was a multicenter, randomized, double-blind, placebo-controlled, pa...
journal_title:Clinical therapeutics
pub_type: 杂志文章,多中心研究,随机对照试验
doi:10.1016/j.clinthera.2005.10.017
更新日期:2005-10-01 00:00:00
abstract::In a double-blind study, 59 patients with chronic erosive gastritis received 50 mg of pirenzepine twice daily and 55 patients received 400 mg of cimetidine twice daily for six weeks. In both groups, days of pain, of heartburn, and of nausea per week were significantly reduced during treatment (P less than 0.01). After...
journal_title:Clinical therapeutics
pub_type: 临床试验,杂志文章,随机对照试验
doi:
更新日期:1989-11-01 00:00:00
abstract:PURPOSE:Hypertension occurs in >50% of US nursing home (NH) residents, but it is unclear which antihypertensive classes offer the best balance of benefits and risks in this population. The objectives of this study were to describe the patterns of antihypertensive medication treatment in this population, focusing on thi...
journal_title:Clinical therapeutics
pub_type: 杂志文章
doi:10.1016/j.clinthera.2020.02.016
更新日期:2020-04-01 00:00:00
abstract::Antihypertensive drugs are commonly prescribed for the treatment of patients with both diabetes and hypertension. However, the role of selected agents in the development of hypoglycemia remains controversial. The main objective of this study was to evaluate the effect of antihypertensive agents on the risk of hypoglyc...
journal_title:Clinical therapeutics
pub_type: 杂志文章
doi:10.1016/s0149-2918(99)80039-3
更新日期:1999-08-01 00:00:00
abstract:PURPOSE:Polycystic ovary syndrome (PCOS) is a metabolic and endocrinal disorder affecting a number of women of reproductive age. We aimed to reveal the correlation between the endocannabinoid system and PCOS, which may provide a new therapeutic target for PCOS treatment. METHODS:Serum levels of anandamide and 2-arachi...
journal_title:Clinical therapeutics
pub_type: 杂志文章
doi:10.1016/j.clinthera.2017.02.007
更新日期:2017-04-01 00:00:00
abstract::The legal right to assert a conscientious objection is reviewed, using as an example the dispensing of abortifacient drugs by pharmacists. The three areas of law that most significantly concern the right to assert a conscientious refusal are employment law, conscience clauses, and religious discrimination law. Each of...
journal_title:Clinical therapeutics
pub_type: 杂志文章
doi:
更新日期:1993-01-01 00:00:00
abstract::The comparative bioavailability of ceftibuten, a new third-generation cephalosporin antibiotic given orally once daily, in capsule and suspension dosage forms, was assessed in healthy male subjects. In three separate studies, subjects received either a 400-mg dose as a suspension or one laboratory-batch, 400-mg capsul...
journal_title:Clinical therapeutics
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1016/s0149-2918(96)80068-3
更新日期:1996-11-01 00:00:00
abstract:BACKGROUND:Etravirine is a non-nucleoside reverse transcriptase inhibitor (NNRTI) with activity against both wild-type HIV and viruses harboring NNRTI resistance. Etravirine is mainly eliminated via the hepatobiliary route. OBJECTIVES:This study in HIV- patients with mild or moderate hepatic impairment and healthy mat...
journal_title:Clinical therapeutics
pub_type: 杂志文章
doi:10.1016/j.clinthera.2010.02.013
更新日期:2010-02-01 00:00:00
abstract::Alzheimer's disease (AD) is a devastating neurodegenerative disorder, with a rapidly increasing worldwide prevalence. Although no cure for AD has yet been found, substantial progress has been made in our understanding of AD pathogenesis. This progress has led to the development of numerous promising compounds in vario...
journal_title:Clinical therapeutics
pub_type: 杂志文章,评审
doi:10.1016/j.clinthera.2013.09.009
更新日期:2013-10-01 00:00:00
abstract::Against the backdrop of the COVID pandemic, the scientific and medical communities are working with all deliberate speed with state-of-the-art technologies to develop diagnostic and therapeutic products that can identify, treat, and prevent infection with SARS-CoV-2. These activities may only be legally conducted with...
journal_title:Clinical therapeutics
pub_type: 杂志文章
doi:10.1016/j.clinthera.2020.06.014
更新日期:2020-08-01 00:00:00
abstract:BACKGROUND:On February 3, 2006, the US Food and Drug Administration (FDA) approved a live, oral, pentavalent (G1-G4, P1[8]) human-bovine reassortant rotavirus vaccine for the prevention of rotavirus gastroenteritis (RVGE) in infants in the United States. The Advisory Committee of Immunization Practices of the Centers f...
journal_title:Clinical therapeutics
pub_type: 杂志文章,评审
doi:10.1016/j.clinthera.2007.12.018
更新日期:2007-12-01 00:00:00
abstract:BACKGROUND:The off-label use of beta-blockers might be prevalent, but no studies have provided empiric data on the off-label use based on utilization data. OBJECTIVE:This secondary data analysis was conducted to describe the trends of off-label use of beta-blockers among ambulatory visits made to office-based physicia...
journal_title:Clinical therapeutics
pub_type: 杂志文章
doi:10.1016/j.clinthera.2006.10.015
更新日期:2006-10-01 00:00:00
abstract:PURPOSE:The aim of this study was to evaluate the effects of a dietary supplement containing primarily an extract of salmon's milt (semen) on symptoms and blood levels of proinflammatory molecules in patients with fibromyalgia syndrome (FMS), a chronic, painful musculoskeletal disease without a distinct pathogenesis or...
journal_title:Clinical therapeutics
pub_type: 杂志文章,多中心研究
doi:10.1016/j.clinthera.2019.05.019
更新日期:2019-08-01 00:00:00
abstract::Hemodynamic and electrophysiologic effects of procainamide, the pharmacokinetic properties of conventional and sustained-release forms of the drug, guidelines for its administration and dosage, and contraindications for and adverse effects of its use are outlined. A review of clinical studies of procainamide therapy c...
journal_title:Clinical therapeutics
pub_type: 杂志文章,评审
doi:
更新日期:1985-01-01 00:00:00
abstract:BACKGROUND:In vitro studies have demonstrated that ticagrelor, an oral antiplatelet agent, is a substrate, activator, and inhibitor of cytochrome P450 (CYP) 3A. Thus, potential CYP3A-mediated drug-drug interactions may occur. OBJECTIVES:The goal of this article was to report study results on the effect of ticagrelor o...
journal_title:Clinical therapeutics
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1016/j.clinthera.2013.06.003
更新日期:2013-07-01 00:00:00
abstract:BACKGROUND:Alzheimer's disease (AD) is estimated to affect up to 11% of those aged > or =65 years in the United States, and the number of patients with AD is predicted to increase over the next few decades as the population ages. The substantial social and economic burden associated with AD is well established, with th...
journal_title:Clinical therapeutics
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1016/s0149-2918(03)80171-6
更新日期:2003-06-01 00:00:00
abstract::The pharmacodynamic parameter that appears to correlate best with a successful therapeutic outcome with beta-lactam antibiotics is the length of time the serum antibiotic concentration remains above the minimum inhibitory concentration (MIC) for the infecting pathogen. By maximizing this parameter, continuous administ...
journal_title:Clinical therapeutics
pub_type: 杂志文章
doi:10.1016/S0149-2918(00)86736-3
更新日期:1999-11-01 00:00:00
abstract:BACKGROUND:Anemia is a common complication of chronic kidney disease (CKD). The approved dosing interval for currently available erythropoiesis-stimulating agents (ESAs) is 2 to 3 times weekly for epoetin alfa (EPO) and every 1 to 2 weeks for darbepoetin alfa (DARB). However, clinicians sometimes use less frequent dosi...
journal_title:Clinical therapeutics
pub_type: 杂志文章
doi:10.1016/j.clinthera.2007.09.012
更新日期:2007-09-01 00:00:00
abstract:PURPOSE:Stroke is the second leading cause of death and the third leading cause of disability worldwide. Diabetes mellitus and the associated hyperglycemia are important risk factors for acute ischemic stroke and are associated with poor prognosis. Neurovascular protection is an important therapeutic target to achieve ...
journal_title:Clinical therapeutics
pub_type: 杂志文章,评审
doi:10.1016/j.clinthera.2020.09.008
更新日期:2020-11-01 00:00:00
abstract:BACKGROUND:Empagliflozin is a sodium glucose cotransporter 2 inhibitor in clinical development as a treatment for type 2 diabetes mellitus. OBJECTIVE:The goal of this study was to investigate potential drug-drug interactions between empagliflozin and verapamil, ramipril, and digoxin in healthy volunteers. METHODS:The...
journal_title:Clinical therapeutics
pub_type: 杂志文章,随机对照试验
doi:10.1016/j.clinthera.2013.02.015
更新日期:2013-03-01 00:00:00
abstract::Inhibitors of platelet glycoprotein (GP) IIb-IIIa have been demonstrated to be effective in controlling acute cardiac complications in patients presenting with acute ischemic coronary syndromes (AICS). Since patients with atherosclerotic coronary vascular disease may present with AICS on multiple occasions, it is impo...
journal_title:Clinical therapeutics
pub_type: 杂志文章
doi:10.1016/S0149-2918(00)88273-9
更新日期:1999-01-01 00:00:00
abstract::Two studies were conducted to determine the prevalence of Chlamydia trachomatis in the urine and cervical exudates of women with genitourinary symptoms. In the first study, 873 women attending the World Health Organization-Sexually Transmitted Disease Center of the Alfred Fournier Institute, in Paris, were examined. I...
journal_title:Clinical therapeutics
pub_type: 杂志文章
doi:
更新日期:1986-01-01 00:00:00
abstract:PURPOSE:Despite the rapid proliferation of hyaluronate (HA) and corticosteroid (CO) injections and clinical guidelines regarding their use in osteoarthritis (OA), information on the characteristics of people receiving these injections is scarce. We describe the use of injections among adults with radiographically confi...
journal_title:Clinical therapeutics
pub_type: 杂志文章
doi:10.1016/j.clinthera.2017.01.006
更新日期:2017-02-01 00:00:00
abstract::In trying to identify the therapeutic impact of a drug, clinical trials eliminate potentially confounding factors such as comorbidities, poor compliance and treatment errors in diagnosis, dosing, and drug interactions. Elimination of these variables means that attempts to use clinical data as the basis for predicting ...
journal_title:Clinical therapeutics
pub_type: 杂志文章
doi:10.1016/0149-2918(95)80098-0
更新日期:1995-11-01 00:00:00
abstract::A national multicentre trial was organized in order to compare the efficacy and safety of leuprorelin acetate depot and danazol in the treatment of endometriosis. Sixty-seven patients with pelvic endometriosis of different severity at laparoscopy were included in the study and followed during the 24 weeks of treatment...
journal_title:Clinical therapeutics
pub_type: 临床试验,杂志文章,多中心研究
doi:
更新日期:1992-01-01 00:00:00
abstract:BACKGROUND:Inhaled dry powder insulin (IDPI) is the first inhaled insulin approved for the treatment of type 1 and type 2 diabetes mellitus (DM). OBJECTIVE:This article reviews available information on IDPI, focusing on its clinical pharmacokinetics, comparative efficacy, tolerability, adverse events, dosage and admin...
journal_title:Clinical therapeutics
pub_type: 杂志文章,评审
doi:10.1016/j.clinthera.2007.05.015
更新日期:2007-05-01 00:00:00
abstract:PURPOSE:Despite the availability of numerous pharmacologic and nonpharmacologic antiseizure therapies, a fraction of patients with epilepsy remain refractory to current treatment options, underscoring the need for novel drugs and neuromodulatory therapies. Transcranial magnetic stimulation (TMS), coupled with either el...
journal_title:Clinical therapeutics
pub_type: 杂志文章,评审
doi:10.1016/j.clinthera.2020.05.016
更新日期:2020-07-01 00:00:00
abstract:OBJECTIVE:The aim of this study was to compare the efficacy and safety of nebulized arformoterol 15 microg/2 mL twice daily (ARF15 BID) and 30 microg/4 mL once daily (ARF30 QD) in subjects with moderate to severe chronic obstructive pulmonary disease (COPD). METHODS:In this single-dose, multicenter, randomized, modifi...
journal_title:Clinical therapeutics
pub_type: 杂志文章,多中心研究,随机对照试验
doi:10.1016/j.clinthera.2009.08.012
更新日期:2009-08-01 00:00:00
abstract:BACKGROUND:In Korea, the treatment of hypertension and dyslipidemia constitutes an important strategy for the prevention of cardiovascular disease (CVD). OBJECTIVE:This study sought to investigate the cost-effectiveness (from the Korean health care system perspective) of prescribing a proprietary formulation single-ta...
journal_title:Clinical therapeutics
pub_type: 杂志文章
doi:10.1016/j.clinthera.2009.10.015
更新日期:2009-10-01 00:00:00
abstract:PURPOSE:Our study evaluated adverse events of therapeutic failure (and specifically reduced duration of action) with the use of a branded product, Osmotic Release Oral System (OROS) methylphenidate, which is approved for the treatment of attention deficit/hyperactivity disorder, and a generic product (methylphenidate, ...
journal_title:Clinical therapeutics
pub_type: 杂志文章
doi:10.1016/j.clinthera.2017.08.018
更新日期:2017-10-01 00:00:00